Method and device to treat kidney disease

ABSTRACT

The invention relates to a method and device for dialysis and or bulk fluid removal by generating a fibrosis chamber within a body cavity and performing dialysis or bulk fluid removal. An implantable medical device is described having a fibrosis chamber and a pump. A dialysis chamber and an optional electrodialysis unit can further be provided. An additional controller uses sensory feedback to regulate the fluid levels by altering the extracellular fluid retention within the fibrosis chamber. This device can be used for the treatment of patients with chronic kidney disease who may also be suffering from cardiorenal syndrome and hypertension.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is filed as a divisional of U.S. Non-provisional patentapplication Ser. No. 13/399,910, filed Feb. 17, 2012. This applicationclaims benefit of priority to U.S. Provisional Patent Application Ser.No. 61/444,092, filed Feb. 17, 2011, which is incorporated herein byreference.

FIELD OF THE INVENTION

The invention relates to a partially or fully implantable medical devicefor dialysis or fluid removal from the peritoneum that overcomesproblems with fibrogenesis and infection. The medical device has apartially porous mesh that forms a fibrosis cage upon implantation intoa patient, an optional dialysis chamber inside the partially porous meshor extracorporeally having an inlet and an outlet, and a pumping meansfor pumping fluid out of the fibrosis cage. The systems and methods ofthe invention optionally include an implantable dialyzer and orelectrodialyzer. The invention further relates to methods of introducinga dialysate directly into a patient and dialyzing blood intracorporeallyor extracorporeally.

BACKGROUND

Kidneys of the human body function to remove excess fluids as well assome ions. The functional unit of the kidney is the nephron. A nephronconsists of a filtering unit of tiny blood vessels called a glomerulusattached to a tubule. When blood enters the glomerulus, it is filteredand the remaining fluid then passes along the tubule. In the tubule,chemicals and water are either added to or removed from this filteredfluid according to the body's needs, and the final product is urine,which is excreted.

In patients with chronic kidney disease, kidney function is severelycompromised. Chronic kidney disease (CKD), also known as chronic renaldisease, is a progressive loss in renal function over a period of monthsor years. The most severe stage of CKD is End Stage Renal Disease(ESRD), which occurs when the kidneys cease to function. The two maincauses of CKD are diabetes and high blood pressure, which areresponsible for up to two-thirds of the cases. Heart disease is theleading cause of death for all people having CKD. Excessive fluid canaccumulate in patients suffering from ESRD. The mortality rate of ESRDpatients who receive traditional hemodialysis therapy is 24% per yearwith an even higher mortality rate among diabetic patients. Fluidaccumulates in ESRD patients because the kidneys can no longereffectively remove water and other fluids from the body. The fluidaccumulates first in the blood and then accumulates throughout the body,resulting in swelling of the extremities and other tissues as edema.This accumulation of fluid causes increased stress on the heart, in turncausing significant increases in blood pressure or hypertension, whichcan lead to heart failure.

Although the population of patients afflicted with CKD grows each year,there is no cure. Current treatments for CKD seek to slow theprogression of the disease. However, as the disease progresses, renalfunction decreases, and, eventually, renal replacement therapy isemployed to compensate for lost kidney function. Renal replacementtherapy entails either transplantation of a new kidney or dialysis.

Methods to treat kidney disease require the processing of blood toextract waste components such as urea and ions. The traditionaltreatment for kidney disease involves dialysis. Dialysis emulates kidneyfunction by removing waste components and excess fluid from a patient'sblood. This is accomplished by allowing the body fluids, usually theblood, to come into the close proximity with the dialysate, which is afluid that serves to cleanse the blood and actively remove the wastecomponents and excess water. During this process, the blood anddialysate are separated by a dialysis membrane, which is permeable towater, small molecules (such as urea), and ions but not permeable to thecells. Each dialysis session lasts a few hours and may be repeated asoften as three times a week.

Traditional processes, such as dialysis, require extracorporealprocessing of body fluids. Once the blood is purified, it is thenreturned to the patient. Although effective at removing waste componentsfrom blood, dialysis treatments are administered intermittently and,therefore, do not emulate the continuous function of a natural kidney.Once the dialysis session is completed, the fluid begins to accumulateagain in the tissues of the patient. The benefits of dialysisnotwithstanding, statistics indicate that three out of five dialysispatients die within five years of commencing treatment. Studies haveshown that increasing the frequency and duration of dialysis sessionscan improve the survivability of dialysis patients. Increasing thefrequency and duration of dialysis sessions more closely resembles thecontinuous kidney function sought to be emulated. However, theextracorporeal processing of the body fluids increases the discomfort,inconvenience and the costs associated with treatment. There is also anadditional risk of infection, which mandates that the procedures becarried out under the supervision of trained medical personnel.

Wearable dialysis units have been conceived in which the variouscomponents of the dialysis unit are miniaturized and made portable. Theutility of these units remains limited due to the requirement that theblood must be brought outside of the body for filtering and due to thenecessity for frequent servicing of the parts.

An alternative to a wearable dialysis system is an implantable dialysisdevice. With conventional implantable dialysis devices, most of thecomponents are implanted, and the blood does not leave the patient'sbody. This type of unit suffers from difficulties related to the needfor surgery to replace the internal parts, generally resulting fromgrowth of tissue over the surfaces of the device that are exposed totissue fluids, which results in reduced efficiency of the filtration.

Another clinical solution for kidney disease is peritoneal dialysis. Inperitoneal dialysis, dialysate is infused into the peritoneal cavity.The peritoneal membrane serves as a natural dialyzer, and wastecomponents diffuse from the patient's bloodstream across the peritonealmembrane into the dialysis solution via an osmotic gradient. Under localanesthesia, a many-eyed catheter is sutured in place in the peritoneumand a sterile dressing is applied. The amount and the kind of dialysateand the length of time for each exchange cycle vary with the age, size,and condition of the patient. There are three phases in each cycle.During inflow, the dialysate is introduced into the peritoneal cavity.During equilibration (swell), the dialysate remains in the peritonealcavity. By means of osmosis, diffusion, and filtration, the neededelectrolytes pass via the vascular peritoneum to the blood vessels ofthe abdominal cavity, and the waste products pass from the blood vesselsthrough the vascular peritoneum into the dialysate. During the thirdphase (drain), the dialysate is allowed to drain from the peritonealcavity by gravity. The dialysis solution is removed, discarded, andreplaced with fresh dialysis solution on a semi-continuous or continuousbasis. Patients are able to replace the fluid periodically and care forthe access ports. This particular treatment causes discomfort due toexcess amounts of fluid being pumped in and out of the abdominal areaand retrograde flow into the bloodstream, which can increase fluidretention and the risk of infections. Further, medication for pain maybe necessary.

Peritoneal dialysis may result in several complications, includingperforation of the bowel, peritonitis, atelectasis, pneumonia, pulmonaryedema, hyperglycemia, hypovolemia, hypervolemia, and adhesions.Peritonitis, the most common problem, is usually caused by failure touse aseptic technique and is characterized by fever, cloudy dialysate,leukocytosis, and abdominal discomfort. There is a need for a dialysissystem for peritoneal dialysis and/or fluid removal that is safe andeffective and that markedly improves a patient's comfort and quality oflife over conventional systems and methods. It would be advantageous forthe system to be safe enough for continuous use and allow the patient tocarry out normal daily activities. Hence, there is an unmet medical needto build a wearable or implantable medical device to treat chronickidney disease that can provide more frequent or continuous treatmentwith less discomfort and a lower risk of infection.

SUMMARY OF THE INVENTION

The invention is directed to a medical device for dialysis within theperitoneum that can be partially or fully implanted. Related medicalsystems and methods for intra-corporeal dialysis are provided.

In one embodiment, a partially implantable medical device has apartially porous mesh that forms a fibrosis cage upon implantation intoa patient, and a pumping means for pumping fluid into and out of thefibrosis cage. In any embodiment, the pumping means can be positionedinside the partially porous mesh, outside the mesh or adjacent to themesh.

In another embodiment, the medical device has a dialysis chamber havingan inlet and an outlet inside of a partially porous mesh.

In another embodiment, the medical device has a pumping means positionedinside the partially porous mesh, outside the mesh or adjacent to theporous mesh.

In another embodiment, the medical device has a partially porous meshthat forms a fibrosis cage upon implantation into a patient, anelectrodialyzer in fluid communication with a dialysis chamber insidethe partially porous mesh, and a pumping means for pumping fluid intoand out of the fibrosis cage.

In another embodiment, the medical device has a partially porous meshthat forms a fibrosis cage upon implantation into a patient, anelectrodialyzer in fluid communication with a dialysis chamber, and apumping means for pumping fluid into and out of the fibrosis cage.

In another embodiment, the medical device has a partially porous meshthat forms a fibrosis cage upon implantation into a patient, anelectrodialyzer in fluid communication with a dialysis chamber, and apumping means for pumping fluid into and out of the fibrosis cage,wherein the pumping means is located outside of the fibrosis cage.

In another embodiment, the medical device has a partially porous meshthat forms a fibrosis cage upon implantation into a patient, a pump thatis placed inside or outside of the partially porous mesh to provide thepumping means for pumping the fluid out of the fibrosis cage, and acatheter to bring the fluid out of the body or a catheter to bring thefluid into the bladder.

In another embodiment, the medical device has a pumping means locatedinside of the fibrosis cage.

In another embodiment, the medical device has a partially porous meshthat forms a fibrosis cage upon implantation into a patient, anelectrodialyzer in fluid communication with a dialysis chamber and theelectrodialyzer outside the partially porous mesh, and a pumping meansfor pumping fluid into and out of the fibrosis cage.

In another embodiment, the medical device has a partially porous meshthat forms a fibrosis cage upon implantation into a patient, anelectrodialyzer in fluid communication with a dialysis chamber and theelectrodialyzer outside the partially porous mesh and the body of apatient, and a pumping means for pumping fluid into and out of thefibrosis cage.

In another embodiment, the medical device has a means for sensing afluid volume of the patient, wherein the means for sensing fluid volumeis an electrical impedance plethysmography or an arterial pressuremeasurement.

In another embodiment, the medical device has a means to deliver freshdialysate to the dialysis chamber.

In another embodiment, the medical device has a controller forregulating the fluid volume of the patent and adjusting a clearance rateof the patient.

In yet another embodiment, the medical device has a partially porousmesh that forms a fibrosis cage upon implantation into a patient, anelectrodialyzer inside the partially porous mesh, and a pumping meansfor pumping fluid into and out of the fibrosis cage.

In a medical system of the invention, one embodiment has a partiallyporous mesh that forms a fibrosis cage upon implantation into a patient,a dialysis chamber inside the partially porous mesh having an inlet andan outlet, a pumping means for pumping fluid into and out of thefibrosis cage, a optional means for sensing a fluid volume of thepatient, an external dialysate cleanser, and a controller such as a pumpcontroller known to those of skill in the art for regulating the fluidvolume and adjusting a clearance rate of the patient.

In another medical system of the invention, one embodiment has apartially porous mesh that forms a fibrosis cage upon implantation intoa patient, an electrodialyzer in fluid communication with a dialysischamber inside the partially porous mesh, a pumping means for pumpingfluid into and out of the fibrosis cage, a optional means for sensing afluid volume of the patient, and a controller for regulating the fluidvolume and adjusting a clearance rate of waste components in thepatient.

In another embodiment, the medical device has a partially porous meshthat forms a fibrosis cage upon implantation into a patient, anelectrodialyzer inside the partially porous mesh, and a pumping meansfor pumping fluid into and out of the fibrosis cage.

In another embodiment, the medical device has a pumping means that is abellows pump.

In another embodiment, the medical device has a pressure sensor todetermine a fluid pressure within the medical device.

In another embodiment, the medical device has a pumping means that ispowered by a rechargeable battery.

In another embodiment, the medical device has a pumping means that ispowered by a rechargeable battery rechargeable through wireless energytransfer.

In another embodiment, the medical device has a dialysate chamber formedin arrays or a layered form.

In another embodiment, the medical device has a catheter to convey fluidfrom inside a dialysis chamber to the urinary bladder of a patient.

In another embodiment, the fibrosis cage of the medical device ispositioned in an abdominal area of the patient, and in front of theperitoneal membrane of the patient.

In another embodiment, the medical device has a fibrosis cage having aporous opening facing the peritoneal membrane of the patient.

In another embodiment, the medical device has an external dialysatecleansing unit containing a sorbent capable of removing waste componentsand ions from dialysate.

In another embodiment, the medical device has a pumping means selectedfrom the group consisting of the pumping means is one selected from thegroup consisting of a bellows pump, a peristaltic pump, a pulsatile pumpand a syringe pump.

In another embodiment, the medical device has a pumping means regulatedto maintain a maximum pressure change of 25 mmHg between the insidevolume of a fibrosis cage of the medical device and the peritonealcavity of a patient.

In another embodiment, the medical device has a pumping means regulatedto not exceed a maximum pressure change of 25 mmHg between the insidevolume of a fibrosis cage of the medical device and the peritonealcavity of a patient.

In another embodiment, the medical device has a pumping means regulatedto not exceed a maximum pressure change of any selected from 5, 15, 20,25, 30, 35, 40, 45 and 50 mmHg, wherein the pressure difference is apressure difference between the inside volume of a fibrosis cage of themedical device and the peritoneal cavity of a patient.

In another embodiment, the medical device has an electrodialyzer thatapplies an electrical field to concentrate ions and waste componentsinto a plurality of chambers using an electrical potential.

In another embodiment, the medical device has an electrodialyzer that isin fluid communication with the patient's urinary bladder.

In another embodiment, the medical device has a means for sensing fluidvolume in a patient wherein the means for sensing fluid volume iselectrical impedance plethysmography or an arterial pressuremeasurement.

In another embodiment, the medical device is used to remove bulk fluidor excess fluid from a patient.

In another embodiment, the medical device has a dialysis chamber and apumping means that function to allow excess fluid from a patient to beremoved from the patient and expelled through an outlet of the dialysischamber.

In another embodiment, the medical device has a dialysis chambercontaining a membrane, wherein the membrane contacts extracellular fluidor bodily fluids of a patient.

In another embodiment, the medical device has a dialysis chamber influid communication with a fibrosis cage, wherein the dialysis chamberis located outside of the fibrosis cage.

In another embodiment, the medical device has a dialysis chamber influid communication with a fibrosis cage, wherein the dialysis chamberis located outside of the body of a patient.

In another embodiment, the medical device has a dialysis chamber,wherein a fresh supply of the dialysate is supplied to the dialysischamber.

In another embodiment, the medical device has a dialysis chamber,wherein a fresh supply of the dialysate is supplied to the dialysischamber and a dialysate exiting an outlet of the dialysis chamber is notcontacted with a sorbent or a dialysate cleansing unit.

In another embodiment, the medical device removes excess fluids frompatients having cardio-renal syndrome. The device has a fibrosis cage, apump within the cage, and a catheter leading to the bladder. The medicaldevice can also have electronics such as a negative pressure sensor anda wireless charger. The medical device can be self-contained and removea few liters of fluid a day from a patient.

In yet another embodiment, a method has the steps of introducing adialysate into a patient in need thereof, and dialyzing bodily fluid orextracellular fluid intra-corporeally. Other embodiments include thesteps of inducing a pressure difference across the peritoneum of apatient to increase the total volume of fluid in an implanted medicaldevice, dialyzing bodily fluids or extracellular fluid across a membraneusing dialysate inside the implanted medical device, and inducing apressure difference across the peritoneum to decrease the total volumeof fluid in the implanted medical device. Still other embodimentscontemplate the step of cleansing the dialysate in a closed loopcleaning process.

In another embodiment, a medical device is applied to the use oftreating a patient by performing a method of treatment, wherein themedical device has a partially porous mesh that forms a fibrosis cageupon implantation into the patient and the fibrosis cage defining aspace for accessing fluid from the patient, and the method of treatmentcomprises inducing a pressure difference across the peritoneum of apatient to increase a total volume of peritoneal fluid in an implantedmedical device and performing one or more steps selected from the groupconsisting of: 1) dialyzing the blood across the peritoneal membrane,wherein peritoneal fluid is conveyed to a space inside of the implantedmedical device and then conveyed to a dialysis chamber having adialysate to reduce the concentration of waste components in theperitoneal fluid conveyed to implanted medical device; 2) dialyzing theblood across the peritoneal membrane, wherein peritoneal fluid isconveyed to an inside of the implanted medical device and then contactedwith a dialysis chamber having dialysate to reduce the concentration ofwaste components in the peritoneal fluid conveyed to the implantedmedical device and using an electrical potential to regenerate thedialysate; and 3) removing excess fluid from the patient by removing atleast part of the fluid from implanted medical device from the patient.The method of treating the patient further includes inducing a pressuredifference across the peritoneum to decrease the total volume of fluidin the implanted medical device and return fluid from inside the medicaldevice to the patient.

In another embodiment, a device is applied to a use for removing wastecomponents or fluid, the device having a partially porous mesh and afibrosis forming surface defining a space for accessing extracellularfluid and a pump for moving extracellular fluid into and out of thespace, the use including reducing the concentration of waste componentsin extracellular fluid or removing extracellular fluid.

In another embodiment, an implantable medical device has a partiallyporous mesh and a fibrosis-forming surface forming a fibrosis cage thatdefines a space for accessing a fluid, wherein the device is capable ofinducing a relative pressure difference inside the fibrosis cage and canperform any one of conveying a fluid to the space inside the implantedmedical device and then conveying the fluid to a dialysis chamber havinga dialysate to reduce the concentration of waste components in the fluidconveyed to the implanted medical device; conveying a fluid to the spaceinside the implanted medical device and then conveying the fluid to adialysis chamber having a dialysate to reduce the concentration of wastecomponents in the fluid conveyed to the implanted medical device andusing an electrical potential to regenerate the dialysate; and removingexcess fluid by removing at least part of the fluid from the implantedmedical device, and also inducing a pressure difference to decrease thetotal volume of fluid in the implanted medical device.

In additional embodiments, dialysis is performed across the membraneusing a pump. In yet another embodiment, the step of expelling aneffluent dialysate extra-corporeally is contemplated. Still yet anotherembodiment has the step of dialyzing bodily fluids or extracellularfluid using an electrical potential and directing the effluent filtrateto the patient's bladder. Other objects, features and advantages of thepresent invention will become apparent to those skilled in the art fromthe following detailed description. It is to be understood, however,that the detailed description and specific examples, while indicatingsome embodiments of the present invention are given by way ofillustration and not limitation. Many changes and modifications withinthe scope of the present invention may be made without departing fromthe spirit thereof, and the invention includes all such modifications.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagram of a partially implantable embodiment of a medicalsystem for removing fluid from the peritoneum of a patient and conveyingthe fluid to the urinary bladder.

FIG. 2 is a partially implantable embodiment of a dialysis system havingan external dialysis unit.

FIG. 3 is a block diagram of a partially implantable embodiment of thedialysis system having an external dialysate cleansing unit.

FIG. 4 is a graphical illustration of the pressure, flow, and volumerelationship that exists during operation of the dialysis system.

FIG. 5 is a block diagram of a fully implantable embodiment of thedialysis system having an internal electrodialysis unit.

FIG. 6 shows the electrodialysis unit of FIG. 5 in greater detail.

FIG. 7 shows an implantable embodiment of a medical system for removingfluid from the peritoneum of a patient and conveying the fluid to theurinary bladder.

FIG. 8 shows the implantable embodiment of FIG. 7 with a wireless powersupply unit for providing power to the medical system.

FIG. 9 shows an exemplary cage formed from stainless steel withpoly(N,N-dimethylacrylamide) (PDMA) end caps and size shown relative toa Japanese 100 yen coin.

FIG. 10 shows an exemplary cage formed from polyester with a fibroticcapsule after implantation for a period of two weeks.

FIG. 11 shows an exemplary cage formed from steel wrapped in polyvinylalcohol (PVA) with a fibrotic capsule after implantation for a period oftwo weeks.

FIG. 12 shows a plot of the diffusion of urea across a polyester cagewith a fibrotic capsule and across a stainless steel cage with afibrotic capsule.

FIG. 13 shows a plot of the diffusion of potassium ions across astainless steel cage wrapped in polyvinyl alcohol (PVA) with a fibroticcapsule.

DETAILED DESCRIPTION OF THE INVENTION

Unless defined otherwise, all technical and scientific terms used hereingenerally have the same meaning as commonly understood by one ofordinary skill in the relevant art.

The articles “a” and “an” are used herein to refer to one or to morethan one (i.e., to at least one) of the grammatical object of thearticle. By way of example, “an element” means one element or more thanone element.

An “adjustable voltage generator” is an electrical component capable ofdelivering and maintaining varying magnitudes of voltage to otherelectronic components. The voltage delivered may be determined by auser, or a programmable control unit.

A “bellows pump” is a pump capable of creating an alternating positiveand negative pressure within a confined space.

“Chronic kidney disease” (CKD) is a condition characterized by the slowloss of kidney function over time. The most common causes of CKD arehigh blood pressure, diabetes, heart disease, and diseases that causeinflammation in the kidneys. Chronic kidney disease can also be causedby infections or urinary blockages. If CKD progresses, it can lead toend-stage renal disease (ESRD), where the kidneys fail completely.

The terms “communicate” and “communication” include, but are not limitedto, the connection of system electrical elements, either directly orremotely, for data transmission among and between said elements. Theterms also include, but are not limited, to the connection of systemfluid elements enabling fluid interface among and between said elements.

The term “comprising” includes, but is not limited to, whatever followsthe word “comprising.” Thus, use of the term indicates that the listedelements are required or mandatory but that other elements are optionaland may or may not be present.

The term “consisting of” includes and is limited to whatever follows thephrase the phrase “consisting of.” Thus, the phrase indicates that thelimited elements are required or mandatory and that no other elementsmay be present.

A “control system” consists of combinations of components that acttogether to maintain a system to a desired set of performancespecifications. The performance specifications can optionally includesensors and monitoring components, processors, memory and computercomponents configured to interoperate.

A “controller” or “control unit” is a device which monitors and affectsthe operational conditions of a given system. The operational conditionsare typically referred to as output variables of the system, which canbe affected by adjusting certain input variables.

The term “dialysate” describes a fluid into which solutes from a fluidto be dialyzed diffuse through a membrane.

“Dialysis” is a type of filtration, or a process of selective diffusionthrough a membrane. In certain embodiments, dialysis removes solutes ofa specific range of molecular weights via diffusion through a membranefrom a fluid to be dialyzed into a dialysate. In other embodiments,dialysis can remove an amount of bulk fluid volume from a subject orpatient by passage of fluid through a membrane due to a pressuredifference across the membrane; the pressure difference can be createdby a pump in some embodiments. In certain embodiments, bulk fluid volumecan be removed from the blood or extracellular fluid to affect fluidremoval from the patient or subject. During dialysis, a fluid to bedialyzed is passed over a filter membrane, while dialysate is passedover the other side of that membrane. Dissolved solutes such as ions,urea, and other small molecules are transported across the filtermembrane by diffusion between the fluids or a volume of fluid crossesfrom one side of the membrane to the other. The dialysate can be used toremove solutes and/or bulk fluid volume from the fluid to be dialyzed,and does not necessarily require the removal of waste via diffusivedialysis.

A “dialysis chamber” as used herein is a chamber in which dialysis isperformed. A dialysis chamber contains or has a dialysis membrane forthe performance of “dialysis” as defined above. The dialysis membranecan be provided in any useful configuration known to those of ordinaryskill in the art including provided as an arrangement of several hollowfibers, tubes, microfibers or microtubes to maximize a ratio betweensurface area of the dialysis membrane and a volume of dialysate. Thedialysis membrane can refer to a semi-permeable barrier selective toallow diffusion of solutes of a specific range of molecular weightsthrough the barrier, or optionally a high-permeability membrane, whichis a type of semipermeable membrane that is more permeable to water thanthe semipermeable membrane of a conventional dialysis membranes having asemipermeable membrane that has a relatively low permeability to water.In certain non-limiting examples, the high-permeability semipermeablemembrane has an in vitro filtration coefficient (Kuf) greater than 8milliliters per hour per conventional millimeter of mercury, as measuredwith bovine or expired human blood while a conventional semipermeablemembrane has a filtration coefficient (Kuf) less than 8 milliliters perhour per convention millimeter of mercury. One of ordinary skill in theart will understand that alternative and various configurations,materials and values in performance and fabrication of the dialysatechamber and/or membrane can be made and used without departing from theinvention.

An “electrodialysis unit” as used herein is a fluid processing unit thatremoves waste components from effluent dialysate by altering the ioniccomposition of a fluid. Such units may include electrically conductiveplates separated by ion-exchange membranes. Fluid flowing between theplates is exposed to an electrical field. The electrical field induces arate of ion movement within the fluid corresponding to the magnitude ofthe voltage potential formed between the electrically conductive plates.

A “dialysate cleansing unit” as used herein is a fluid processing unitthat removes waste components from effluent dialysate via sorbentadsorption.

The term “effluent dialysate,” as used herein describes the discharge oroutflow after the dialysate has been used for dialysis.

A “fibrosis cage(s)” as used herein describes a fibrogenic mesh encasedin fibrotic tissue and having an empty internal cavity containing thecomponents of the implantable medical device as well as bodily fluids.

The term “filtration” refers to a process of separating solutes from afluid, by passing the fluid through a filter medium across which thesolutes cannot pass.

The term “implantable,” as used herein describes a device, component ormodule intended to be totally or partially introduced, surgically ormedically into a mammalian body, or by medical intervention that remainsafter the procedure.

The term “hyperosmotic” pertains to a solution that has a higher soluteconcentration than another solution. In the human body, a hyperosmoticstate refers to a condition caused by the accumulation in the body ofsignificant quantities of osmotically active solutes.

The term “hypoosmotic” pertains to a solution containing a lowerconcentration of osmotically active components than a standard solution.In the human body, a hypoosmotic state describes a cell that has a lowerconcentration of solutes than its surroundings.

The term “intracorporeal,” as used herein means existing within thebody.

Osmolarity is defined as the number of osmoles of a solute per liter ofsolution. Thus, a “hyperosmolar solution” represents a solution with anincrease in osmolarity compared to physiologic solutions. Certaincompounds, such as mannitol, may have an effect on the osmoticproperties of a solution as described herein.

The term “mesh” or “porous mesh” refers to a porous substructure thatcan be optionally wrapped in a material that blocks the passage ofcells. The “mesh” or “porous mesh” creates or defines an acellular spaceor substantially acellular space within the body of the patient, wherethe “mesh” or “porous mesh” allows for the passage or diffusion of ions,urea and other small molecules, and water while substantially preventingthe passage of cells. The “mesh” or “porous mesh” creates or defines anacellular space from which fluid can be removed from the patient orfluid from the peritoneum can be treated by dialysis or electrodialysis.

A “patient” is a member of any animal species, preferably a mammalianspecies, optionally a human. The subject can be an apparently healthyindividual, an individual suffering from a disease, or an individualbeing treated for a disease.

A “pressure gauge” is a device that measures pressure, which is theforce per unit area applied in a direction perpendicular to the surfaceof an object. Gauge pressure is the pressure relative to the localatmospheric or ambient pressure.

The term “programmable” as used herein refers to a device using computerhardware architecture and being capable of carrying out a set ofcommands, automatically.

The term “sensory unit” refers to an electronic component capable ofmeasuring a property of interest.

The term “total volume of fluid” refers to the total volume ofextracellular fluid and dialysate within the medical device or fibrosiscage. The total volume of fluid can be controlled, in some embodiments,through a pump or pump means that modifies the volume of spaceaccessible to extracellular fluid and/or dialysate within the medicaldevice or fibrosis cage. Specifically, in some embodiments, a pump orpump means can increase the volume of space to affect an influx ofdialysate and/or extracellular fluid within the medical device orfibrosis cage and a pump or pump means can decrease the volume of spaceto affect an efflux of dialysate and/or extracellular fluid from themedical device.

The terms “treating” and “treatment” refer to the management and care ofa patient having a pathology or condition. Treating includesadministering one or more embodiments of the present invention toprevent or alleviate the symptoms or complications or to eliminate thedisease, condition, or disorder. As used herein, “treatment” or“therapy” refers to both therapeutic treatment and prophylactic orpreventative measures. “Treating” or “treatment” does not requirecomplete alleviation of signs or symptoms, does not require a cure, andincludes protocols having only a marginal or incomplete effect on apatient.

The term “waste components” as used herein describe waste organic andinorganic components, such as urea, uric acid, creatinine, chlorides,inorganic sulfate and phosphate. Specific “waste components” can varybetween individual depending on diet and environmental factors. Hence,the term is intended to encompass any waste component that is normallyremoved by a kidney or by dialysis without restriction on the specifictype of waste.

A “wearable dialyzer” is a portable artificial kidney device throughwhich blood is circulated as the user moves through his daily routine,the dialyzing fluid being regenerated by a system of filters and make-upsolids continuously fed to the dialysis fluid. The device may be acontinuously internally operable and externally regenerable dialysisdevice that is capable of concurrently dialyzing a confined dialysisfluid against body fluids within the body and regenerating the dialysisfluid outside the body.

Implantable Peritoneal Cage

The present invention can be used for the treatment of chronic kidneydisease, either as a replacement for a failed organ, or to reduce theneed for dialysis. Furthermore, it can be configured to work as astand-alone system wherein ambulatory dialysis is carried out by thesystem, or as an auxiliary system for hospital dialysis systems.

The present invention can employ a fibrosis cage, a pumping means, andan optional dialysis chamber. Further, the present invention canoptionally employ a sensory unit, a controller, and an electrodialysisunit.

Referring to FIG. 1, an embodiment of a system for removing fluid fromthe body of a patient is described. A fibrosis cage 1 is formed byimplanting a partially porous fibrogenic mesh 1 into a patient's body 2.The mesh can be treated with a surface coating of fibrosis-inducingagents, or extracellular matrix components which promote the growth offibrous tissue. The mesh can also be covered with a material that isimpermeable to cells, such as a sheet of polyvinyl alcohol (PVA). Themesh can also be impregnated with a slow-release pharmacological agentwhich controls fibrous tissue growth. For example, pharmacologicalagents that promote or inhibit fibrous tissue growth can be used. Thefibrosis cage is preferably located in the patient's abdominal area, infront of the peritoneal membrane 3. During a maturation period afterimplantation, the fibrogenic mesh 1 promotes the growth of a fibroustissue (shown below) which encapsulates the mesh thereby forming thefibrosis cage. The fibrosis cage has a porous opening facing theperitoneal membrane 3 through which extracellular fluid enters the cage.The peritoneal membrane 3 is represented by a dashed line in FIG. 1 toillustrate the boundary between the peritoneal fluid and the blood ofthe patient. After the maturation period, a space inside the fibrosiscage is mostly void of cellular matter, and is full of extracellularfluid from the peritoneum. Such cellular matter includes red bloodcells, white blood cells, polymorphonuclear neutrophils, macrophages,and lymphocytes.

As illustrated in FIG. 1, in order to expedite the diffusion of fluid inand out of the cage, a pump or pumping means 7 is provided. The pump orpumping means 7 is not limited to any particular type of pump or anyparticular location. In certain embodiments, the pump or pumping means 7is located outside of the cage 1. In some embodiments, the non-limitingpump or pumping means 7 can be a bellows pump, a peristaltic pump, asyringe pump or a pulsatile pump. The pump or pumping means 7 forcesfluid in and out of the cage periodically via expansion and contractionor another pumping mechanism. The pump or pumping means 7 can be drivenby an implanted rechargeable battery, or an externally supplied magneticfield. In certain embodiments, the rechargeable battery is rechargeableby wireless energy transfer. An optional pressure gauge can be presentto monitor the fluid pressure within the fibrosis cage. A controller 18can be present to control the operation of the pump or pumping means 7.The controller 18 can in certain embodiments be located outside the body2 of the patient and can communicate with the pump or pumping means 7wirelessly.

In certain embodiments, the pump or pumping means 7 is located inside ofthe peritoneal cage. The pump or pumping means 7 can be provided inlocations outside of the fibrosis cage. In some embodiments the pumpingmeans 7 can be placed adjacent to the cage in a manner where the pump orpumping means 7 can modulate the pressure within the fibrosis cage. Inother embodiments, the pump or pumping means 7 can be connected to thefibrosis cage through any suitable means. In still other embodiments,the pump or pumping means 7 can be connected to the cage with tubing.The pump or pumping means 7 can optionally be connected to a catheterentering into the urinary bladder.

In FIG. 1, fluid is removed from the patient by means of the pump orpumping means 7 drawing extracellular fluid from the peritoneum of thepatient into the cage 1 and transporting at least part of the fluiddrawn into the cage 1 to the urinary bladder 20 by means of a catheter22 connecting the cage 1 and the urinary bladder 20. As such, fluid canbe removed from the patient using an implantable system without the needfor providing a supply of dialysate. In an alternate embodiment, thecatheter 22 or another means can be used to remove fluid from the cage 1extracorporeally without discharge to the bladder 20. That is, thecatheter 22 or equivalent structure can pass out of the body through aport or incision such that fluid is discarded or collected outside ofthe body.

Referring to FIG. 2, a fibrosis cage 1 as in FIG. 1 is formed byimplanting a partially porous fibrogenic mesh 1 into a patient's body 2.In FIG. 2, the system is provided to perform dialysis on the patient'sblood via the peritoneal fluid. The system in FIG. 2 has a dialysischamber with a membrane for performing dialysis, wherein fluid from theperitoneum via the implanted cage 1 is contacted with one side of themembrane and a dialysate is contacted with the other side of themembrane. Waste components diffuse across the membrane inside thedialysis chamber from the peritoneum to the dialysate. The fluid fromthe peritoneum having a reduced concentration of waste components isreturned to the peritoneum cavity 24. Due to the removal of wastecomponents from the peritoneal fluid, waste components diffuse from theblood of the patient across the peritoneum membrane 3. That is, thesystem shown in FIG. 2 removes waste components from the peritoneumfluid to maintain a concentration gradient in waste components betweenthe patient's blood and the peritoneal fluid across the peritonealmembrane 3.

As shown in FIG. 2, a dialysis unit 30 is provided extracorporeally influid communication with the implanted cage 1. An outlet tube 34 ispresent connecting the dialysis unit 30 and an outlet 36 of theimplanted cage 1. Similarly, an inlet tube 38 is present connecting thedialysis unit 30 and an inlet 32 of the implanted cage 1. Outlet tube 34and inlet tube 38 enter the body through an incision or port 40 locatedon the body 2 of the patient. The dialysis chamber (not shown) can bepresent inside the dialysis cage 1 or the dialysis unit 30. In certainembodiments where the dialysis chamber is present in the implanted cage1, the pump or pumping means 7 causes the influx and outflux of fluidfrom the peritoneum into the implanted cage 1 and the dialysis unit 30provides a dialysate that is moved through the dialysis chamber insidethe implanted cage 1. Due to the contact of the peritoneum fluid and thedialysate across the membrane in the dialysis chamber, waste componentsdiffuse from the peritoneum of the patient to the dialysate. Further, ahydrostatic pressure difference across the membrane can cause theremoval of fluid from the peritoneum and the patient. The dialysis unit30 provides a source of dialysate including optionally a pump or othermeans to convey dialysate through the dialysis chamber. A supply offresh dialysate can be provided wherein spent dialysate is discardedafter passage through the dialysis chamber or a dialysate cleansing unit(described below) can be provided within the dialysis unit 30 toregenerate fresh dialysate from the dialysate exiting the cage 1 throughoutlet 36.

In other embodiments of the system shown in FIG. 2, the dialysis chamberis located within the dialysis unit 30. In such embodiments, peritonealfluid is drawn into the implanted cage 1 through action of the pump orpumping means 7, which can be positioned intra- or extracorporeally. Theperitoneal fluid is directed through outlet 36 and into outlet tube 34to the dialysis unit 30 and dialysis chamber wherein the peritonealfluid removed from the patient is dialyzed with a dialysate. Theperitoneal fluid removed from the patient via the implanted cage 1 isthen returned to the patient through the inlet tube 38 and inlet 32.Optionally, at least part of the peritoneal fluid removed from thepatient can be discarded and not returned to the patient in order tocause a net removal of fluid from the patient. A supply of freshdialysate can be provided wherein spent dialysate is discarded afterpassage through the dialysis chamber or a dialysate cleansing unit(described below) can be provided within the dialysis unit 30 toregenerate fresh dialysate from previously used dialysate. As describedbelow, in any embodiment an electrodialysis unit can be provided toregenerate effluent dialysate from the dialysis chamber.

Referring to FIG. 3, an embodiment of a dialysis system according to thepresent invention having an optional external dialysate cleaning unitand a dialysis chamber within the implanted cage 1 is described. In someembodiments, a supply of fresh dialysate can be supplied in lieu of theoptional external dialysate cleaning unit. A fibrosis cage is formed byimplanting a partially porous fibrogenic mesh 1 into a patient's body 2.The mesh can be treated with a surface coating of fibrosis-inducingagents, or extracellular matrix components which promote the growth offibrous tissue. The mesh can also be covered with a material that isimpermeable to cells, such as a sheet of polyvinyl alcohol (PVA). Themesh can also be impregnated with a slow-release pharmacological agentthat controls fibrous tissue growth. For example, pharmacological agentsthat promote or inhibit fibrous tissue growth can be used. The fibrosiscage is preferably located in the patient's abdominal area, in front ofthe peritoneal membrane 3. During a maturation period afterimplantation, the fibrogenic mesh 1 promotes the growth of a fibroustissue 6 which encapsulates the mesh thereby forming the fibrosis cage.The fibrosis cage has a porous opening 4 facing the peritoneal membrane3 through which extracellular fluid enters the cage. After thematuration period, a space 5 inside the fibrosis cage is mostly void ofcellular matter, and is full of extracellular fluid. Such cellularmatter includes red blood cells, white blood cells, polymorphonuclearneutrophils, macrophages, and lymphocytes. An alternative location tothe abdominal area for the cage is inside the peritoneal cavity, whichitself has low number of cells, thus rendering space 5 of the cage witheven less cellular matter therein.

In certain embodiments, the fibrosis cage can be formed by two layers ofmaterials. The first layer of material can be a metal or a plasticconfigured into a substructure that provides structural integrity to theoverall device. The substructure is formed into any configuration suchthat passage of fluid through the substructure is unimpeded while thestructural integrity of the substructure is maintained. In certainnon-limiting embodiments, the substructure is formed into a mesh, ahoney-comb, or any arrangement of evenly or unevenly spaced openingsbetween which fluids can flow. Additionally, the first layer of materialcan be formed into a cage that prevents the collapse of the device underthe pressure from the organs of the body. The substructure also allowsthe device to be able to sustain a negative pressure in the inner cavityof the device. The second layer of material is optional and can be acoating used to cover the fibrosis cage. Since the coating may not havea requisite structural strength, the coating can rely on thesubstructure to remain in place over the substructure. Due to thecontact of the coating with tissue, the biocompatibility of the coatingmaterial is important. In particular, the coating material should notcause very thick fibrosis, should allow for the passage of fluids andions, and should remain impermeable to the passage of cells. Manysuitable materials known to those of ordinary skill can be used for thecoating such as dialysis bags and woven polyesters. One particularlypreferred material is poly vinyl alcohol (PVA) foam. A suitable,non-limiting thickness for a coating constructed from a PVA foam can befrom about 1 mm to about 10 mm.

To demonstrate the feasibility of accessing bodily fluids using afibrosis cage, a rodent model was implanted with stainless steel orpolyester cages. Stainless steel cages were built in the shape ofcylinders with a diameter of 1 cm and the ends of the cylinders werecapped with Polydimethylsiloxane (PDMS). Afterwards, the stainless steelcages were wrapped in a sheet of polyvinyl alcohol (PVA) and the cageswere sterilized using alcohol. The resulting devices were implantedsubcutaneously in the backs of rats, two for each rat, for periods ofone to five weeks. At the end of the study, animals were sacrificed andthe devices were removed. Gross pathological examination of theexplanted devices showed that there was about 1 mm thick fibroticcapsule formation around the device. Further examination indicated thatthe inside of the cage was cell and tissue free. As further describedbelow, in vitro studies done using the explanted cages surrounded byfibrotic tissues showed that water, urea, sodium chloride and potassiumchloride were all capable of diffusion through the fibrotic capsules andthe cage walls.

As such, the fibrosis cage can be applied to a use of removing wastecomponents, including urea and ions, from a fluid includingextracellular fluid. Once waste components and/or fluid are present inan inside space of the fibrosis cage, the waste components can beremoved by contact with a dialysis chamber, which can be located insidethe fibrosis cage, or by the fluid containing the waste components beingconveyed to a dialysis chamber at another location. The fibrosis cagecan be further applied to the use of returning fluid without wastecomponents or with a lowered concentration of waste components. As such,the fibrosis cage can be applied to the use of dialysis of the blood bylowering the concentration of waste components in the peritoneum.Alternatively, the fibrosis cage can be applied to the use of removingfluid from the peritoneum. Still further, the fibrosis cage can beapplied to the use of removing fluid from the peritoneum and therebyremoving fluid from the blood and other body compartments.

During the maturation period, a fibrous tissue 6 builds over the cagewithin a few weeks, leaving the inner space 5 acellular. As illustratedin FIG. 3, in order to expedite the diffusion of fluid in and out of thecage 1, a pump or pumping means 7 is placed therein or at anotherlocation. The pump or pumping means 7 is not limited to any particulartype of pump. In some embodiments, the non-limiting pump or pumpingmeans 7 can be a bellows pump, a peristaltic pump, a syringe pump, animpeller pump, a pulsatile pump, or any other suitable pump known tothose of ordinary skill One non-limiting example of an impeller typepump has an impeller rotatably positioned inside a housing wherein theimpeller generates a rotating torque to enable movement of fluid. Thepump or pumping means 7 forces fluid in and out of the cage 1periodically via expansion and contraction or via another pumpingmechanism. As shown in FIG. 3, a diaphragm 45 can be provided as part ofthe pump or pumping means 7 to assist in moving fluid in and out of thecage 1. The pump or pumping means 7 can be driven by an implantedrechargeable battery, or an externally supplied magnetic field. Incertain embodiments, the rechargeable battery is rechargeable bywireless energy transfer. An optional pressure gauge 12 can monitor thefluid pressure within the fibrosis cage 1.

In certain embodiments, a dialysis chamber 8 within the fibrosis cage 1is placed in front of the pump or pumping means 7 and remains inconstant contact with the extracellular fluid from the peritoneum thatis flowing in and out of the cage. In certain embodiments, due to thereduction in the concentration of waste components in the extracellularfluid, a concentration gradient between the blood and extracellularfluid across the peritoneal membrane is maintained to drive the dialysisof waste components from the blood across the peritoneal membrane 3. Inother embodiments, bulk movement of fluid volume from the blood to theextracellular fluid, which can then be removed by the medical device,occurs across the peritoneal membrane 3 to assist bulk removal of fluidfrom a subject or patient. The dialysis chamber 8 includes a dialysismembrane across which exchange between a dialysate solution andextracellular fluid within space 5 occurs. The dialysate from thedialysis chamber 8 can be regenerated using an optional dialysatecleansing unit. Alternatively, a fresh supply of dialysate can besupplied to the dialysis chamber 8 to maintain a concentration gradientbetween the dialysate and the extracellular fluid. That is, in certainembodiments dialysis across a dialysis membrane is performed byproviding a fresh supply of a dialysate to the dialysis chamber 8wherein the dialysate is not regenerated by treatment with a sorbent ora dialysate cleansing unit.

The system shown in FIG. 3 performs dialysis by circulating a dialysatesolution through the dialysis chamber 8 via inlet port 9 and outlet port10 of the dialysis chamber 8. During dialysis, waste components in theextracellular fluid from the peritoneum contained within the fibrosiscage are transported by diffusion across the dialysis membrane of thedialysis chamber 8 to the dialysate. Effluent dialysate exits thedialysis chamber 8 via outlet port 10 and enters an optional externaldialysate cleansing unit 11. The optional external dialysate cleansingunit 11 contains sorbents which are used to remove waste components suchas urea and ions from the dialysate. The structure of the externaldialysate cleansing unit 11 and sorbents is not limited provided thatwaste components are removed from effluent dialysate. In someembodiments, sorbents similar to the REDY sorbent system can be used.Roberts M. The regenerative dialysis (REDY) sorbent system, Nephrology4:275-278, (1998). The dialysate cleansing unit 11 can also be providedin the dialysis unit 30 described in FIG. 2. Waste components includeurea, potassium ions and various nitrate ions. The sorbent packages arecartridges which can be replaced by the patient when saturated by wastecomponents. Once cleansed, the dialysate exits the external dialysatecleansing unit 11 and returns to the dialysate chamber 8 to continuedialysis. In an alternate embodiment, a supply of fresh dialysate issupplied to the dialysis chamber 8 and a dialysate cleansing unit is notpresent. That is, the dialysate exiting outlet 10 is discarded andreplenished with fresh dialysate solution.

Referring now to FIG. 5, another embodiment of a dialysis systemaccording to the present invention having an electrodialysis unit isdescribed. The embodiment of FIG. 5 is similar to that of FIG. 3, exceptthe embodiment of FIG. 5 does not include an external sorbent-baseddialysate cleansing unit, and instead includes an electrodialysiscleansing unit 13. FIG. 5 shows an electrodialysis cleansing unit 13located internal to the fibrosis cage 1. In other embodiments, anelectrodialysis cleansing unit 13 can also be provided in the embodimentdescribed in FIG. 2 either inside the cage 1 or inside the dialysis unit30. The embodiment of FIG. 5 also includes an optional catheter 14 fordischarge of waste components to a patient's bladder or removed from thepatient's body and either discarded or optionally treated

In the embodiment of FIG. 5, dialysate cleansing is accomplished byelectrodialysis. The electrodialysis unit 13 generates a pseudo urineand discharges it into the bladder via a catheter 14 or removed from thepatient's body and either discarded or optionally treated. Theelectrodialysis unit 13 operates by applying direct current (“DC”)electrical fields to the dialysate in order to change the osmolarity ofthe solution. The electrodialysis unit includes an adjustable voltagegenerator to generate electrical fields of varying magnitudes forselective removal of waste components.

In alternate embodiments, the electrodialysis cleansing unit 13 islocated outside of the fibrosis cage and can be located outside of thebody of the patient, such as in the dialysis unit 30 as shown in FIG. 2.In such embodiments, dialysate from the outlet port 10 of the dialysischamber 8 is transported to an external electrodialysis unit (not shown)where the dialysate is treated. The dialysate can then either be treatedby electrodialysis or the dialysate can be partially discarded with theremainder of the dialysate treated by electrodialysis. Then, the treateddialysate is retuned via the inlet port 9 of the dialysis chamber 8. Thetransport of dialysate from the dialysis chamber 8 to theelectrodialysis unit can be accomplished by the pump or pumping means 7or by an additional pumping means.

Referring to FIG. 6, the electrodialysis unit 13 of FIG. 5 is shown ingreater detail. Effluent dialysate enters the electrodialysis chambervia inlet port 10. Electrical fields generated by a power source 15create an electric potential which drives movement of the ions toconcentrate them in different chambers. Hypoosmotic dialysate exits theelectrodialysis unit via outlet port 9 while a hyperosmotic dialysatesolution is discharged into the urinary bladder or removed from thepatient's body and either discarded or optionally treated via outletport or catheter 14. The hypoosmotic dialysate returns to the dialysatechamber 8 of FIG. 5 to continue dialysis.

By adjusting the electric potential generated by the power source 15,the osmolarity of the solutions can be controlled, permitting regulationof fluid and salt removal from the dialysate, and in turn from thepatient. The device can be built as a completely implantable system, andcan be powered by an internal or external power source, or a combinationof an internal and external power source. Power sources may includeimplanted batteries or an external magnetic field. A programmablecontroller can regulate fluid and salt extraction and flow rates throughthe system.

In both of the embodiments shown by FIGS. 3 and 5, the growth offibrotic tissue over the dialysis chamber 8 is prevented because thedialysis chamber is located inside the fibrosis cage. This in turnprolongs the useful life of the dialysis chamber 8 and provides a safeenvironment for dialysis to take place. Furthermore, by physicallyisolating the dialysate from the body, the risk of infection is reduceddramatically. In the event that a pathogen was to enter the dialysischamber 8, the pathogen would not be able to pass through the dialysismembrane and infect the patient.

In an additional embodiment, the implanted cage and the pump within areused to extract fluid from the body and to direct the extracted fluid tothe urinary bladder to treat fluid overload in a patient with heartfailure or cardio-renal symptoms, as shown in FIG. 1. This embodimentcan be totally implantable within the patient, where a drainage catheterconnects the fibrosis cage to the urinary bladder for conveyance ofextracted fluid to the urinary bladder. Optionally, the conveyance ofthe extracted fluid from the fibrosis cage to the urinary bladder can beassisted and/or controlled with an additional pump. To reduce thecalcification of the drain catheter, piezoelectric vibrators can beplaced around the catheter and periodically excited. Piezoelectricvibrators can also be provided in association with catheter 14 and 22 asshown in FIG. 1 or 5. Operation of the device in this embodiment can beopen loop to extract a certain amount of fluid each day, governed by thepatient based on a personal feedback mechanism such as body weight, orcontrolled by an electronic unit and its optional feedback sensor suchas electrical impedance monitor indicating the body fluid level.

An alternate embodiment is shown in FIG. 7, which depicts a completelyimplantable implementation of the system. The fibrosis cage 1 withfibrotic capsule 6 is used to accumulate fluid within the device cavity5 and fluid from the device cavity 5 is removed via the outlet 36. Pump42, shown as external to the fibrosis cage 1, is used both for thegeneration of the negative pressure inside the device cavity 5 and alsoto pump the fluid via the outlet 36. Fluid is finally disposed into theurinary bladder 20 via the catheter 22. The pumping action commencesonly when the controller 18 determines that the pressure inside thedevice cavity 5 is equal of more than −25 mm Hg. Pressure sensing isdone by the pressure gauge 12. Additionally, the piezoelectric vibrators44 are activated by the controller 18 to reduce calcification on theinner walls of the catheter 23. In this embodiment, all components areimplanted and power can be supplied via an external unit 47 shown inFIG. 8. Implementation depicted in FIG. 8 shows an embodiment where thepump 42 is located internal to the fibrosis cage where other elementsare as described in FIG. 7.

In alternate embodiments of the system shown in FIG. 7, the catheter 22or another means can be used to remove fluid from the cage 1extracorporeally. That is, the catheter 22 or equivalent structure canpass out of the body through a port or incision such that fluid isdiscarded or collected outside of the body.

Embodiments of the dialysis system preferably include an electroniccontroller. The electronic controller can be used to maintain pressurewithin the system by regulating the total volume of fluid within thefibrosis cage. Additionally, the controller can adjust the dialysis rateof the system. The electronic controller may include a programmablecontrol unit. A control feedback system may be formed by electrical orwireless data links between a control unit, pump or pump means 7 and thepressure gauge 12. A programmable control unit 18 is shown in FIGS. 1and 2. Systems and methods for establishing communication between anexternal device and an implanted medical device have been developed,such as those described in U.S. Pat. No. 7,023,359, Goetz et al., thesubject matter of which is incorporated herein by reference.

The control unit can also be able to detect a fluid overload situationwithin the system. In the event of fluid overload, the control unitreduces the volume of dialysate in the system in order to extractadditional amounts of fluid from the patient. The electronic controllerregulates the flow of dialysate through the dialysis chamber 8, and alsomonitors the amount of dialysate present in the dialysis chamber. Apatient's fluid status can be measured using a variety of means, such aselectrical impedance plethysmography and arterial pressure measurements.

The efficacy of dialysis performed by embodiments of the dialysis systemis governed in part by the presence of cellular matter within thefibrosis cage. The presence of cellular matter within a dialysis systemnegatively influences diffusive mass transfer therein. Thus it ispreferable to have a system which limits the presence of cellular matterin order to maintain the effectiveness of dialysis performed by thesystem.

The medical devices and methods described herein are not limited to thetreatment of humans. Rather, the medical devices and methods describedherein can be applied to other mammals including cats and dogs and otheranimals commonly kept as pets but also including exotic pets. Notably,cats oftentimes require dialysis as treatment for end-stage renaldisease (ESRD). The terms “subject” and “patient” as used throughoutthis document include humans as well as other non-human mammals.Non-limiting examples of non-human mammals include monkeys, rabbits,gerbils, guinea pigs, hamsters, chinchillas, ferrets, mice, rats, pigs,horses, felines, canines, primates, hedgehogs, rodents, polecats, fennecfoxes, tame silver foxes, red foxes, skunks, raccoons, capybaras,hedgehogs, arctic foxes, bears, coyotes, wolves and wolf/dog hybrids.

It is known that a pressure of (−)25 mmHg lower body negative pressure(“LBNP”) is tolerated by humans. In certain embodiments, the pump orpumping means 7 is regulated not to exceed a maximum LBNP or pressuredifference between the internal volume of the fibrosis cage of themedical device and the peritoneal cavity, for example, 25 mmHg. However,other non-limiting ranges for maximum pressure difference can include10-50, 15-25, 17-29, 12-45, 23-28, and 21-38 mmHg. In some embodiments,the maximum pressure difference can be any one of 5, 15, 20, 25, 30, 35,40, 45 and 50 mmHg. In further embodiments, the pump or pumping means 7is regulated not to exceed a maximum LBNP or pressure difference withinthe medical device selected from any of 5, 10, 15, and 20 mmHg. Thepumping means 7 can also be regulated to not exceed a maximum pressuredifference of any one of 5, 15, 20, 25, 30, 35, 40, 45 and 50 mmHg.Furthermore, it is also known that the active peritoneal flow isapproximately 30 mL/hr/cm-H₂O or 40 mL/hr/mmHg. Therefore, flow ratethrough the peritoneal membrane can be calculated as:

Flow=25 mmHg×40 mL hr⁻¹ mmHg⁻¹=1 L/hr

Since the flow must be reversed periodically to empty the chamber, theactual flow rate would be half of 1 L/hr, or 0.5 L/hr, yielding amaximum daily flow rate of 12 L/day.

In order to limit the pressure generated by the pump or pumping means 7,a pressure gauge 12 is utilized. During the generation of the positiveand negative pressures that are necessary for the pumping action, therelative pressure change is measured and pumping is paused when theabsolute value of the pressure change exceeds 25 mmHg. FIG. 4 shows agraphical representation of the pressure changes inside the fibrosiscage, fluid flow in and out of the cage, and fluid volume within thecage. As discussed above, a control unit in electrical or wirelesscommunication with the pump or pumping means 7 and pressure gauge 12 maybe used to regulate the pressure of fluid within the fibrosis cage.

It will be apparent to one skilled in the art that variations of thepresent invention are possible. For example, the dialysis chamber 8 canbe constructed in layers, and additional layers can be used to increasethe efficacy of dialysis. Modifications to the shape of the cage and theinternal structures such as the pump or pumping means 7 can also beincorporated to improve the system dialysis function, anatomical fit,and cosmetic appearance of the device.

It will also be apparent to one skilled in the art that variouscombinations and/or modifications and variations can be made in thedialysis system depending upon the specific needs for operation.Moreover, features illustrated or described as being part of oneembodiment may be used on another embodiment to yield a still furtherembodiment.

EXAMPLE

Cylinder shaped cages were formed using stainless steel and polyestermeshes. Ends of the cylinders were capped using poly(N,N-dimethylacrylamide), also known as PDMA. A picture of the stainlesssteel cage can be seen in FIG. 9. The size the cage in FIG. 9 is shownrelative to a Japanese 100 yen coin. Some of the cages were wrapped inpoly vinyl alcohol (PVA) sheets. All cages were sterilized by dippingthem in alcohol prior to implantation.

Cages were subcutaneously implanted into rats on the back of theanimals. Animals were anesthetized with ethyl ether and small incisionswere made to place two cages in the back of each animal. Two weeks afterthe implantation of the cages, the animals were sacrificed and the cageswere removed. As shown in FIGS. 10 and 11, the cages developed fibroticcapsules during the two weeks of implantation. FIG. 10 shows anexemplary cage formed from a polyester mesh having a fibrotic cage. FIG.11 shows an exemplary cage formed from stainless steel wrapped in PVAprior to implantation having a fibrotic cage.

Procedures were carried out in vitro to measure the diffusion propertiesof the explanted device with its associated fibrotic capsule. First, oneof the PDMA caps was removed to verify that the cages were free oftissue growth within the cage. After verification of the absence ofinternal tissue growth, the cages were partially inserted intohyperosmotic solutions to measure the changes in the concentrations ofsolutes within the cavity of the cages. Care was taken to keep the openend of the cage (having the PDMA cap removed) above the level of thehyperosmotic solution to prevent the solution from entering the cage bya route other than by diffusion across the fibrotic capsule.

Two measurements were carried out to measure the diffusion properties ofthe fibrotic capsule. In the first study, the cage and the surroundingfibrotic capsule were partially immersed into a hyperosmotic ureasolution. Periodically, fluid samples were taken from the inside of thecage to measure the urea concentration inside the cage. The results fromthis study are shown in FIG. 12, where the internal urea concentration(mM) increases as a function of time, which indicates that urea diffusesacross the fibrotic capsule and the cage. Data for both a polyester cageand a stainless steel cage with PVA (PVA cage) are shown in FIG. 12.

In the second study, the diffusion of potassium ions was measured (mM)using a hyperosmotic potassium solution for a stainless steel cage withPVA and a surrounding fibrotic capsule. The procedure was the same as inthe first study except a potassium chloride solution was provided. Asshown in FIG. 13, potassium ions also diffuse across the fibroticcapsule and the cage.

Table 1 below shows the expected number of red blood cells (“RBC”) andwhite blood cells (“WBC”) in a patient's blood and peritoneal cavity.The values in Table 1 reflect typical ranges found in healthyindividuals. As shown in Table 1, the cellular concentration issubstantially reduced in the peritoneal cavity compared with the bloodfor all individuals regardless of physiological or disease state. Assuch, placement of the device in the peritoneal space or at a locationhaving access to the peritoneal space reduces exposure to blood cells.Table 2 shows an exemplary reduction in counts of white blood cells,polymorphonuclear neutrophils (“PMN”), macrophages (“MP”), andlymphocytes (“LYMP”) in a cage over the course of three weeks followingimplantation of the cage. Marchant et al., In vivo BiocompatibilityStudies I: The Cage Implant System and a Biodegradable Hydrogel, J.Biomed. Mat. Res. 17:301-25 (1983).

TABLE 1 Expected cell counts in the blood and peritoneal cavity RBC WBCBlood 4.2-6.9 million/μL 4,300-10,800/μL Peritoneum <10,000/μL <500/μL

TABLE 2 Cell count (cells/μL) interior to an implanted cage with timeDay Total WBC PMN MP LYMP 1 21600 20100 220 1300 3 11000 10100 170 770 44160 3500 110 570 5 2890 2080 84 720 7 820 390 43 390 8 730 180 60 49011 450 42 70 340 14 260 12 14 230 17 250 4 11 240 21 120 2 14 100

1. A method, comprising the steps of: inducing a pressure difference across the peritoneum of a patient to increase a total volume of peritoneal fluid in an implanted medical device, performing one or more steps selected from the group consisting of: 1) dialyzing the blood across the peritoneal membrane, wherein peritoneal fluid is conveyed to a space inside of the implanted medical device and then conveyed to a dialysis chamber having a dialysate to reduce the concentration of waste components in the peritoneal fluid conveyed to the implanted medical device; 2) dialyzing the blood across the peritoneal membrane, wherein peritoneal fluid is conveyed to an inside of the implanted medical device and then contacted with a dialysis chamber having dialysate to reduce the concentration of waste components in the peritoneal fluid conveyed to the implanted medical device and using an electrical potential to regenerate the dialysate; and 3) removing excess fluid from the patient by removing at least part of the fluid from the implanted medical device from the patient, and inducing a pressure difference across the peritoneum to decrease the total volume of fluid in the implanted medical device and return fluid from inside the medical device to the patient.
 2. The method of claim 1, further comprising the step of cleansing the dialysate in a closed loop.
 3. The method of claim 1, further comprising the step of directing at least part of the peritoneal fluid to the patient's urinary bladder.
 4. The method of claim 1, wherein the dialysis chamber or an electrodialyzer for using an electrical potential to regenerate the dialysate is located extracorporeally.
 5. The method of claim 4, wherein the electrodialyzer further comprises an adjustable voltage generator to generate electrical fields of varying magnitudes for selective removal of waste components.
 6. The method of claim 3, further comprising a pump to assist and/or control flow of the peritoneal fluid through a catheter to the patient's urinary bladder.
 7. The method of claim 6, further comprising piezoelectric vibrators placed adjacent to the catheter to reduce calcification of the catheter.
 8. The method of claim 1, further comprising regenerating the dialysate from the dialysis chamber using a dialysate cleansing unit.
 9. The method of claim 8, wherein the dialysate cleansing unit comprises sorbent packages.
 10. The method of claim 9, wherein the sorbent packages are replaceable.
 11. The method of claim 1, further comprising supplying a fresh supply of dialysate to the dialysate chamber.
 12. The method of claim 1, wherein the implanted medical device comprises a partially porous mesh that forms a fibrosis cage upon implantation into a patient, the fibrosis cage defining a space for accessing fluid from the patient.
 13. The method of claim 12, wherein the mesh is treated with at least one of a surface coating of fibrosis-inducing agents, and extracellular matrix components to promote growth of fibrous tissue.
 14. The method of claim 12, wherein the implanted medical device further comprises a pumping means for pumping fluid into and out of the fibrosis cage.
 15. The method of claim 12, wherein the fibrosis cage further comprises a material impermeable to cells surrounding the partially porous mesh.
 16. The method of claim 14, wherein the pumping means is one selected from the group consisting of a bellows pump, a peristaltic pump, a pulsatile pump, an impeller pump, and a syringe pump, said pump means positioned inside the partially porous mesh, outside the partially porous mesh or adjacent to the partially porous mesh.
 17. The method of claim 14, wherein the pumping means is regulated to not exceed a maximum pressure difference of any one of 5, 15, 20, 25, 30, 35, 40, 45 and 50 mmHG, wherein the pressure difference is a pressure difference between the inside of the fibrosis cage and a peritoneal cavity of a patient.
 18. The method of claim 1, wherein the implanted medical device further comprises a controller for regulating the fluid volume of the patient and adjusting a clearance rate of the patient.
 19. The method of claim 1, wherein the implanted medical device further comprises a means for sensing a fluid volume of the patient, wherein the means for sensing fluid volume is an electrical impedance plethysmography or an arterial pressure measurement.
 20. The method of claim 1, wherein the implanted medical device is powered by any selected from the group consisting of an internal battery, an externally coupled power source and a rechargeable battery wherein the rechargeable battery is rechargeable by wireless energy transfer. 